CN110747241A - Preparation method of 2,2, 4-trimethyl-1, 2-dihydroquinoline - Google Patents
Preparation method of 2,2, 4-trimethyl-1, 2-dihydroquinoline Download PDFInfo
- Publication number
- CN110747241A CN110747241A CN201810815521.0A CN201810815521A CN110747241A CN 110747241 A CN110747241 A CN 110747241A CN 201810815521 A CN201810815521 A CN 201810815521A CN 110747241 A CN110747241 A CN 110747241A
- Authority
- CN
- China
- Prior art keywords
- yeast
- dihydroquinoline
- trimethyl
- reaction
- solvent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
- C12P17/10—Nitrogen as only ring hetero atom
- C12P17/12—Nitrogen as only ring hetero atom containing a six-membered hetero ring
Abstract
The invention belongs to the technical field of fine chemical engineering, and relates to a preparation method of 2,2, 4-trimethyl-1, 2-dihydroquinoline. Adding isobutyraldehyde or 4-methyl-2, 3-pentanedione into a specific biotransformation system by using yeast as a biocatalyst, culturing at 0-50 deg.C for 10-1000 min, and centrifuging to remove thallus to obtain fermentation broth; adding a solvent into the fermentation liquor for extraction, then adding aniline, heating to the reaction temperature, reacting for a certain time, and distilling to remove the solvent to obtain the 2,2, 4-trimethyl-1, 2-dihydroquinoline. According to the invention, strong acid is not used as a catalyst, the processes of liquid alkali neutralization and water diversion are not needed, namely, no wastewater is generated, a biotransformation mode is used, the yeast can be reused, and the problem that the raw material acetone is volatile in the reaction process is solved, so that the reaction temperature is reduced, the reaction time is shortened, and the environment-friendly synthesis process is formed.
Description
Technical Field
The invention relates to a preparation method of an anti-aging agent TMQ monomer 2,2, 4-trimethyl-1, 2-dihydroquinoline, which is an enzyme-chemical method for synthesizing 2,2, 4-trimethyl-1, 2-dihydroquinoline with low cost and high yield in a biocatalysis manner, is environment-friendly and relatively cheap, and belongs to the technical field of biocatalysis organic synthesis.
Background
2,2, 4-trimethyl-1, 2-dihydroquinoline is a monomer of an anti-aging agent TMQ, is mainly used for further polymerizing to obtain a di-, tri-or tetra-polymer (anti-aging agent TMQ) of the 2,2, 4-trimethyl-1, 2-dihydroquinoline, also called anti-aging agent RD, the anti-aging agent TMQ is a ketoamine anti-aging agent, is a faint yellow to ruined poise color particle or sheet, is mainly used as a rubber anti-aging agent, has the annual demand of 10 million tons in China, and is one of rubber anti-aging agent products with the largest demand in domestic and foreign markets,
the raw materials for synthesizing the 2,2, 4-trimethyl-1, 2-dihydroquinoline mainly comprise aniline and acetone, the condensation reaction is carried out under the action of an acid catalyst to directly obtain reaction liquid containing the 2,2, 4-trimethyl-1, 2-dihydroquinoline, and the reaction liquid is neutralized by liquid alkali and distilled to obtain the 2,2, 4-trimethyl-1, 2-dihydroquinoline with higher purity.
CN102010369 discloses a method for continuously preparing 2,2, 4-trimethyl-1, 2-dihydroquinoline, aniline and acetone are continuously fed into a reaction tower filled with a solid acid catalyst, and a reactant containing TMQ is overflowed and extracted. CN105348189A discloses a method for continuously preparing antioxidant RD monomer 2,2, 4-trimethyl-1, 2-dihydroquinoline. Adding aniline into a reactor, heating to 80-160 ℃, and reacting aniline, acetone and an acid catalyst according to a molecular ratio of 1-10: 5-100: 1, maintaining the temperature of the reactor at 80-160 ℃, and continuously extracting a condensation reaction liquid containing 2,2, 4-trimethyl-1, 2-dihydroquinoline from a discharge hole at the upper part of the reactor. The method also uses acid catalyst, especially hydrochloric acid, and has the disadvantages of high equipment corrosion and high three-waste treatment cost.
At present, the synthesis methods of 2,2, 4-trimethyl-1, 2-dihydroquinoline related at home and abroad do not relate to the improvement of intermediates in the reaction process, and the methods all use p-aniline and acetone as raw materials. Because the generation of 2,2, 4-trimethyl-1, 2-dihydroquinoline in the synthesis reaction depends on the generation of a key intermediate product 4-methyl-3-pentene-2-ketone obtained after condensation of two molecules of acetone, and the reaction speed of 4-methyl-3-pentene-2-ketone and aniline is very slow, the synthesis method can not completely eliminate the association of a plurality of unpredictable and interpretable side reactions caused by high temperature (120 ℃) and long reaction time and low-boiling point reaction raw material acetone which is too volatile and has low conversion rate and large acetone consumption and long-time high temperature, and is difficult to separate, the purity of the obtained 2,2, 4-trimethyl-1, 2-dihydroquinoline is not high, and 2 is further obtained, the content of TMQ finished products obtained by distilling and separating the 2, 4-trimethyl-1, 2-dihydroquinoline polymer is between 40 and 70 percent, and simultaneously, the defects that a large amount of waste water and waste residues need to be treated and the like are caused.
Disclosure of Invention
The invention aims to overcome the defects of the prior art, synthesize a key precursor in the condensation reaction with aniline, solve the problem that the substitute raw material acetone is volatile in the reaction process, reduce the reaction temperature, shorten the reaction time, form a green and environment-friendly synthesis process without using strong acid as a catalyst, and realize the environment-friendly production of 2,2, 4-trimethyl-1, 2-dihydroquinoline. By avoiding side reaction, the conversion rate of the aniline is greatly improved, so that the production cost of the product is reduced. As a corollary, another object of the present invention is to provide a process for reducing the aniline content in the reaction product to below 1% by weight, to achieve a content standard above 97% without rectification, for direct sale as a product or for the synthesis of high content of the antioxidant TMQ.
The invention provides a preparation method of 2,2, 4-trimethyl-1, 2-dihydroquinoline. The preparation method is realized by the following steps:
adding isobutyraldehyde or 4-methyl-2, 3-pentanedione into a specific biotransformation system by using yeast as a biocatalyst, culturing at 0-50 deg.C for 10-1000 min, and centrifuging to remove thallus to obtain fermentation broth; adding a solvent into the fermentation liquor for extraction, then adding aniline, heating to the reaction temperature, reacting for a certain time, and distilling to remove the solvent to obtain the 2,2, 4-trimethyl-1, 2-dihydroquinoline.
The biological conversion refers to a process of catalyzing isobutyraldehyde or 4-methyl-2, 3-pentanedione to generate a reaction product by using an enzyme system special for yeast at a certain temperature and under a certain pressure.
The yeast refers to yeast varieties such as baker's yeast and beer yeast. The biotransformation system is a mixture of water, reducing sugars and phosphate together with yeast.
The water system refers to tap water or deionized water with certain pH value regulated, and the pH value is within the range of 2-12.
The reducing sugars are various carbon sources that can be utilized by yeasts such as glucose and maltose.
The phosphate salts include various phosphate salts such as sodium hydrogen phosphate, sodium dihydrogen phosphate, and dipotassium hydrogen phosphate.
Further, the operation condition of the centrifugation is centrifugation for 10-600min at the rotation speed of 1000-20000rpm and at 0-50 ℃.
The solvent used may be toluene, xylene, methylene chloride, sulfolane and other organic solvents.
The reaction temperature is 20-200 ℃, and the reaction time is 0.1-20 hours.
Temperatures below 30 c, coupled with longer reaction times, may give higher yields than higher temperature, shorter time processes. A preferred time period for the synthesis of 2,2, 4-trimethyl-1, 2-dihydroquinoline to be substantially complete in the present invention is about 1 to 6 hours. After the synthesis of 2,2, 4-trimethyl-1, 2-dihydroquinoline, the reaction mixture was cooled and physically separated.
Has the advantages that: according to the invention, strong acid is not used as a catalyst, the processes of liquid alkali neutralization and water diversion are not needed, namely, no wastewater is generated, a biotransformation mode is used, the yeast can be reused, and the problem that the raw material acetone is volatile in the reaction process is solved, so that the reaction temperature is reduced, the reaction time is shortened, and the environment-friendly synthesis process is formed.
The conversion rate of the aniline is greatly improved by avoiding side reaction, the content of the aniline in the 2,2, 4-trimethyl-1, 2-dihydroquinoline is reduced to below 1 wt%, the content of a reaction product can reach more than 97% without rectification, the aniline can be directly sold as a product or used for a process for synthesizing a high-content anti-aging agent TMQ, and the production cost is greatly reduced.
Detailed Description
The present invention will be described in detail with reference to examples. It should be noted that the embodiments and features of the embodiments in the present application may be combined with each other without conflict.
Example 1
200g of sucrose, 25g of disodium hydrogen phosphate and 8g of commercially available baker's yeast are added into 2000g of tap water to form a mixture, the mixture is cultured for 40min at 30 ℃ under the condition of continuous stirring, 114g of 4-methyl-2, 3-pentanedione liquid is added into the mixture after the baker's yeast enters a vigorous growth period, after the mixture is continuously cultured for 100min at 30 ℃, the mixture is centrifuged (8 ℃, 10000rpm and 35min) to remove thalli, 500g of toluene is added, extraction and liquid separation are carried out, a water phase is removed, 93g of aniline is added into an oil phase of a toluene layer, a small amount of zeolite is added, the temperature is raised to 120 ℃ for reaction for 4 hours, and the solvent is removed by distillation, so that 174g of 2,2, 4-trimethyl-1, 2-dihydroquinoline with the content of 98.
Example 2
200g of sucrose, 25g of disodium hydrogen phosphate and 8g of commercially available beer yeast are added into 2000g of tap water to form a mixture, then the mixture is cultured for 40min at 30 ℃ under the condition of continuous stirring, 72g of isobutyraldehyde is added into the mixture after the beer yeast enters a vigorous growth period, after the mixture is continuously cultured for 100min at 3 ℃, the mixture is centrifuged (3 ℃, 10000rpm and 35min) to remove thalli, 500g of toluene is added, extraction and liquid separation are carried out, the water phase is removed, 94g of aniline is added into the oil phase of the toluene layer, a small amount of zeolite is added, the temperature is raised to 110 ℃ for reaction for 6 hours, and the solvent is removed by distillation, so that 173g of 2,2, 4-trimethyl-1, 2-dihydroquinoline with the content of 98.5 percent is obtained.
Example 3
The main operating conditions were the same as in example 1, but changing the reducing sugar to maltose, the aniline conversion was determined to be 100.0%, yielding 175g of 2,2, 4-trimethyl-1, 2-dihydroquinoline having a content of 98.0%.
Examples 4 to 19
The experimental procedure of example 1 was used. The product content of the reaction and the aniline conversion were examined by changing the conditions such as the kind of sugar and yeast solvent and the reaction temperature and reaction time during the reaction without changing other conditions, and the results are shown in the following table:
the above description is only a preferred embodiment of the present invention, and is not intended to limit the present invention, and it will be apparent to those skilled in the art that various modifications and variations can be made in the present invention, such as changing the conversion conditions of the biological system and the reaction material ratio of aniline, etc. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. A preparation method of 2,2, 4-trimethyl-1, 2-dihydroquinoline is characterized by comprising the following steps: adding isobutyraldehyde or 4-methyl-2, 3-pentanedione into a biotransformation system by using yeast as a biocatalyst, culturing at 0-50 deg.C for 10-1000 min, and centrifuging to remove thallus to obtain fermentation broth; adding a solvent into the fermentation liquor for extraction, then adding aniline, heating for reaction, and distilling to remove the solvent to obtain the 2,2, 4-trimethyl-1, 2-dihydroquinoline.
2. The method according to claim 1, wherein the yeast is selected from the group consisting of baker's yeast and brewer's yeast.
3. The method according to claim 1 or 2, wherein the bioconversion system catalyzes a reaction product by chemically converting isobutyraldehyde or 4-methyl-2, 3-pentanedione using an enzyme system specific to yeast.
4. The method according to claim 1, wherein the biotransformation system comprises a mixture of water, reducing sugars and phosphates together with yeast.
5. The method according to claim 4, wherein the reducing sugars are various carbon sources available to glucose and maltose.
6. The method according to claim 4, wherein the phosphate is selected from the group consisting of sodium hydrogen phosphate, sodium dihydrogen phosphate and dipotassium hydrogen phosphate.
7. The method according to claim 1, wherein the water is tap water or deionized water adjusted to pH 2 to 12.
8. The method as claimed in claim 1, wherein the centrifugation is performed at 0-50 ℃ and 1000-20000rpm for 10-600 min.
9. The method according to claim 1, wherein the solvent is selected from the group consisting of toluene, xylene, methylene chloride, and sulfolane.
10. The process according to claim 1, wherein the reaction temperature is 20 to 200 ℃ and the reaction time is 0.1 to 20 hours.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810815521.0A CN110747241B (en) | 2018-07-24 | 2018-07-24 | Preparation method of 2, 4-trimethyl-1, 2-dihydroquinoline |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810815521.0A CN110747241B (en) | 2018-07-24 | 2018-07-24 | Preparation method of 2, 4-trimethyl-1, 2-dihydroquinoline |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110747241A true CN110747241A (en) | 2020-02-04 |
| CN110747241B CN110747241B (en) | 2023-05-02 |
Family
ID=69275215
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810815521.0A Active CN110747241B (en) | 2018-07-24 | 2018-07-24 | Preparation method of 2, 4-trimethyl-1, 2-dihydroquinoline |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110747241B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113444039A (en) * | 2021-08-02 | 2021-09-28 | 河南省科学院高新技术研究中心 | Method for preparing 2,2, 4-trimethyl-1, 2-dihydroquinoline by using ionic liquid |
| CN114315713A (en) * | 2020-10-10 | 2022-04-12 | 中石化南京化工研究院有限公司 | Preparation method of low primary amine TMQ (tetramethylammonium terephthalate) antioxidant |
| CN114315712A (en) * | 2020-09-27 | 2022-04-12 | 中石化南京化工研究院有限公司 | Method for purifying 2,2, 4-trimethyl-1, 2-dihydroquinoline polymer |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1344753A (en) * | 2001-10-30 | 2002-04-17 | 中国石化集团南京化工厂 | Solventless one-step process of synthesizing 2,2,4-trimethyl-1,2-dihydroquinoline polymer |
| CN101275153A (en) * | 2007-03-26 | 2008-10-01 | 张丽丽 | Enzyme-chemical method for synthesizing ethoxyquinoline |
| CN102918009A (en) * | 2011-01-26 | 2013-02-06 | 住友橡胶工业株式会社 | Synthesis system, rubber chemical substance for tires, synthetic rubber for tires, and pneumatic tire |
| CN105348189A (en) * | 2014-08-20 | 2016-02-24 | 中国石油化工股份有限公司 | Continuous 2,2,4-trimethyl-1,2-dihydroquinoline preparation method |
| CN108003095A (en) * | 2016-10-28 | 2018-05-08 | 中国石油化工股份有限公司 | A kind of antioxidant TMQ and preparation method thereof |
-
2018
- 2018-07-24 CN CN201810815521.0A patent/CN110747241B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1344753A (en) * | 2001-10-30 | 2002-04-17 | 中国石化集团南京化工厂 | Solventless one-step process of synthesizing 2,2,4-trimethyl-1,2-dihydroquinoline polymer |
| CN101275153A (en) * | 2007-03-26 | 2008-10-01 | 张丽丽 | Enzyme-chemical method for synthesizing ethoxyquinoline |
| CN102918009A (en) * | 2011-01-26 | 2013-02-06 | 住友橡胶工业株式会社 | Synthesis system, rubber chemical substance for tires, synthetic rubber for tires, and pneumatic tire |
| CN105348189A (en) * | 2014-08-20 | 2016-02-24 | 中国石油化工股份有限公司 | Continuous 2,2,4-trimethyl-1,2-dihydroquinoline preparation method |
| CN108003095A (en) * | 2016-10-28 | 2018-05-08 | 中国石油化工股份有限公司 | A kind of antioxidant TMQ and preparation method thereof |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114315712A (en) * | 2020-09-27 | 2022-04-12 | 中石化南京化工研究院有限公司 | Method for purifying 2,2, 4-trimethyl-1, 2-dihydroquinoline polymer |
| CN114315713A (en) * | 2020-10-10 | 2022-04-12 | 中石化南京化工研究院有限公司 | Preparation method of low primary amine TMQ (tetramethylammonium terephthalate) antioxidant |
| CN114315713B (en) * | 2020-10-10 | 2024-01-30 | 中石化南京化工研究院有限公司 | Preparation method of low primary amine TMQ (TMQ) anti-aging agent |
| CN113444039A (en) * | 2021-08-02 | 2021-09-28 | 河南省科学院高新技术研究中心 | Method for preparing 2,2, 4-trimethyl-1, 2-dihydroquinoline by using ionic liquid |
| CN113444039B (en) * | 2021-08-02 | 2022-05-31 | 河南省科学院高新技术研究中心 | Method for preparing 2,2, 4-trimethyl-1, 2-dihydroquinoline by using ionic liquid |
Also Published As
| Publication number | Publication date |
|---|---|
| CN110747241B (en) | 2023-05-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7507561B2 (en) | Process for the production of polylactic acid (PLA) from renewable feedstocks | |
| CA2653028C (en) | Method for the enzymatic production of 2-hydroxy-2-methyl carboxylic acids | |
| US9822335B2 (en) | Amycolatopsis sp. strain and methods of using the same for vanillin production | |
| JP3502419B2 (en) | Method for producing lactic acid and lactic acid ester | |
| Makishima et al. | Development of continuous flow type hydrothermal reactor for hemicellulose fraction recovery from corncob | |
| CN110747241A (en) | Preparation method of 2,2, 4-trimethyl-1, 2-dihydroquinoline | |
| WO2007092898A2 (en) | Process for converting anhydrosugars to glucose and other fermentable sugars | |
| US11060118B2 (en) | Production of vanillin by fermentation | |
| CN109371069B (en) | Method for preparing 5-hydroxymethylfurfural and polyalcohol from xylose mother liquor | |
| CN102633642B (en) | Method for preparing pleuromutilin crystal | |
| CN115181761A (en) | Method for producing sebacic acid by microbial fermentation method | |
| CN110451684B (en) | Treatment method of wastewater of dodecanol ester production process | |
| EP3057931B1 (en) | Ammonium bisulfate catalyzed dehydration of beta-hydroxy acids | |
| WO2012142326A1 (en) | A method of producing 5-hydroxypyridine-2-carboxylic acid from alginate | |
| JPWO2012081112A1 (en) | Method for producing purified lactic acid solution | |
| CN112522351A (en) | Synthetic method of guanine | |
| CN102409068A (en) | Preparation method for (3aS, 6aR)-biotin chiral lactone | |
| CN115725116B (en) | Method for producing epoxy plasticizer by taking lignocellulose biomass as raw material | |
| CN109761949B (en) | Industrial preparation method of 2, 2-dimethyl-4-hydroxymethyl-1, 3-dioxolane | |
| Paranthaman et al. | Production on tannin acyl hydrolase from pulse milling by-products using solid state fermentation | |
| CN112941117A (en) | Method for synthesizing L-lactide from chiral L-lactic acid produced by using lignocellulose biomass as raw material | |
| CN116926138A (en) | Process for producing acrylamide based on controllable speed of microbiological method | |
| CN112679502A (en) | Method for green recovery of adenine from adenosine crude product mother liquor | |
| CN113816836A (en) | Enzymatic production method of (S) -1- (4-chlorphenyl) -1, 3-propylene glycol | |
| WO2016022073A2 (en) | Bacterial strain |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |